Applying for grant awards has not been a problem for the 2016 Ramsay Award winners
As we know, grant applications in chronic fatigue syndrome (ME/CFS) are hard to come by. Freedom of Information Requests indicate that the NIH received the lowest number of ME/CFS grant applications in memory last year – just 15. Since the NIH spends MUCH more money on medical research than any other organization, and since it spends most of its money on individual grant applications, ME/CFS desperately needs researchers to apply for grant applications on its behalf. For the most part, they’re not doing that.
How nice, then, to find an initiative that’s turning out to be something of a grant application machine. The group of 2016 Ramsey Award winners, funded by the Solve ME/CFS Initiative (SMCI), are pumping out grant applications and getting follow up studies funded. The applications are not all directed at the NIH, but they indicate that the 2016 Ramsay Awards have spawned a cadre of eager investigators – and that’s exactly what we need in this field.
Hitting Pilot Study Gold – Twice
I see these awards as critical to jump starting new lines of research. Jarred Younger
With the Jarred Younger Ramsay Award the SMCI got two things – an accomplished researcher who’s shown he can get big NIH grants and a creative researcher who’s been able to successfully explore new pathways in ME/CFS.
Younger, who leads the Neuroinflammation, Fatigue and Pain Lab at the University of Alabama at Birmingham, wasn’t always the major ME/CFS researcher he is now, though. Back in 2011 Younger was mostly a fibromyalgia researcher known for his low dose naltrexone studies. Then a seed grant from Stanford’s Institute of Immunity, Transplantation and Infection, pushed him into this field.
That small grant award produced the pilot data for his novel “Good Day/Bad Day” study which suggested that the immune system was likely driving the fatigue in ME/CFS – a rather significant finding after years of inconsistent cytokine studies. Younger had found a way to show that the immune system was deeply involved in ME/CFS and was able to flip that pilot data over into a large NIH funded, 5-year ME/CFS study that’s underway now.
Younger’s Ramsey award study provided evidence for one of the most sought after findings in ME/CFS – it suggested that neuroinflammation is not just present but is elevated virtually everywhere in the brains of people with ME/CFS.
Armed with that knowledge, Younger was able to score another grant from the Scottish non-profit MERUK to look for the source of the neuroinflammation – an immune cell invasion of the brain.
Because he was also able to apply his new technology to traumatic brain injury (TBI) and rheumatoid arthritis patients, we now know another startling fact: the neuroinflammation in ME/CFS, at least thus far, appears to be distinct. Neuroinflammation was restricted to certain areas of the brain in TBI and wasn’t present at all in rheumatoid arthritis (RA) – a shocking finding given the high levels of fatigue in RA. The data strongly suggests that fatigue is produced in different ways in different diseases – from the central nervous system inflammation in ME/CFS to something happening in the periphery or the body in RA.
Younger quickly applied for an NIH grant to expand the neuroinflammation study, bring in more disease groups, see what an exercise stressor will do to the brains of ME/CFS patients and other evaluations. He’s already got an answer. The NIH wants to redo the grant application and add something to the study (a PET scan group). Yes, the NIH is actually asking Younger to ask for more money…
It’s hard to believe Younger won’t get that grant award, and when he does, it will constitute a massive return on investment for the SMCI and the ME/CFS community. The SMCI put in about $50K and the ME/CFS community will get out something like $3,000,000.
Younger is optimistic about the future. He believes that the next few years will bring an objective and reliable diagnostic tool for a large subgroup of patients. That will accelerate the research and provide new treatment targets which, with the biomarker in place, can be efficiently pursued.
Small grant awards have allowed Younger to strike gold twice in the ME/CFS field, and they’ve brought us a major new researcher. The SMCI’s goal (and our goal as a community) is to find more Youngers: more researchers who are able to flip small grant awards into major projects and become prominent members of our field.
Let’s see what else the 2016 Ramsay Award winners may bring…How about a successful international collaboration that combined two of the hottest fields in ME/CFS research?
International Multidisciplinary Collaboration Works
The Cambridge, Mensah and Armstrong Project
Fane Mensah came to the ME/CFS field much the same way Younger came to fibromyalgia – he wanted a field he could make a big difference in. He met Chris Armstrong on a Young Researcher panel, compared notes, decided that someone in the field really should combine the immune system and metabolomics (and it might as well be them), and then with the encouragement of then SMCI director, Zaher Nahle, submitted a grant proposal.
Mensah, Cambride and Armstrong merged two fields to come up with results which are prompting further study
The proposal was prompted by the early Rituximab findings, which we now know were false positives, but which only makes the group’s findings all the more interesting. Although the Rituximab findings didn’t work out, the groups study did. Using a new technique, the team found that the B-cells in ME/CFS patients were unusually activated and were demonstrating odd metabolic behavior to boot – a pattern that could have implications for autoimmunity.
With their new way to understand B-cell behavior set up, the next step for the group is to give the B-cells in ME/CFS a real workout. They’re going to tweak those cells with a variety of stressors, metabolites, B cell activators, metabolic pathway inhibitors and cytokines and see how they respond metabolically and immunologically.
This Ramsey award resulted in another grant award from another program and will be providing further insights into the immune-metabolic interface in ME/CFS. Plus we have two new young researchers in the field. Score another success for the 2016 Ramsey Awards.
The Herpesvirus Mitochondria Connection
HHV-6 is another almost ubiquitous herpesvirus which the body can’t get rid of and which has taken up residence in many people’s cells. There it lingers for the most part at low levels, doing no harm. The body seems to keep it in check.
Bhupesh Prusty is not so sure. He has the novel idea that a herpesvirus like HHV-6/7 may have found a way of turning off the mitochondria. Since HHV-6 typically resides in nervous system tissues, an abrupt downregulation of the mitochondria in those cells could obviously have profound effects. Prusty, like Robert Naviaux, believes the mitochondria are the place to go to determine the health of a cell.
In this Ramsay Award study, Prusty used high-end, super resolution microscopic imaging to study the mitochondrial dynamics and function in HHV-6 infected cells. His goal was nothing less than to figure out how HHV-6 manages to hijack the mitochondria of the cells they infect.
That was achieved, but then came the REALLY interesting part. Prusty found HHV-6 in about 60% of a small group of ME/CFS patients’ cells, but the viral loads found were thought to be too low to produce disease. What came next was astonishing. Prusty found that one HHV6 infected ME/CFS cell was able to alter the mitochondrial functioning of neighboring, or even distant cells – apparently by secreting mitochondrial inhibitors.
Prusty’s work suggested HHV-6 infected cells may be emitting something into the blood which affects the energy production of other cells.
If Prusty is right, you don’t need to have a massive HHV-6 infection to cause problems; you just need a moderate HHV-6 infection that then turns off other nearby cells. It’s a doubly intriguing idea given Ron Davis’ and Oystein Fluge’s findings suggesting that something in the plasma is turning ME/CFS ‘ patients’cells into couch potatoes! It also seems to accord well with Robert Naviaux’s dauer effect.
Furthermore, Prusty believes, viruses other than HHV-6 may be doing the same thing. Prusty’s findings clearly have the potential to cause the medical profession to rethink the impact that viral infections can have. Given the infectious trigger so common in ME/CFS, that sounds like a very good thing to have happen.
One paper has come out of the pilot study and several more are in the works. Plus, Prusty is applying for a grant (from a German fund) to expand his work. Next he hopes to further nail down the molecular pathway HHV-6 uses to whack a cell’s mitochondria in hopes of finding a treatment target.
Prusty’s work makes one wonder if Younger may have underestimated the number of biomarkers this field may achieve over the next couple of years.
Score another win for the 2016 Ramsay Awards.
The Case For Autoimmunity
Very little acceptance of ME/CFS exists in Germany. Even though the doctors there are clearly in the dark ages, some rays of light exist, and the brightest is coming from Dr. Carmen Scheibenbogen, an MD and PhD at Charité –Universitätsmedizin Berlin.
Somehow Dr. Scheibenbogen has managed to become one of the most prolific ME/CFS researchers of the last five years. Her success indicates that a dedicated researcher given funding can make a real difference in this field – no matter where she or he is working from. She is hopefully a sign of things to come.
Scheibenbogen is using her Ramsay Award to build the case or an autoimmune subset in ME/CFS
Scheibenbogen is best known for her autoimmune work in ME/CFS. However, that work, while potentially groundbreaking, was missing something. Autoimmunity isn’t just about auto-antibodies. People with autoimmune diseases commonly display other tweaks in their system. This study was about building the case for autoimmunity in ME/CFS by showing that a subset of ME/CFS patients display those tweaks.
It involved demonstrating that the genetic variants in B cells, T cells and/or cytokines (TNF-α expression, IFN type I, IL-12R) that are typically involved in an autoimmune response are also present in people with ME/CFS. Doing so could potentially open the door to more funding and eventually new treatment options for a large subset of patients.
The good news is that Dr. Scheibenbogen used her Ramsay Award to do just that. She found a promising autoimmune genetic signature in her ME/CFS patients. Her next step is to do a larger study to confirm the initial findings.
Sheibenbogen work has put her on the path, like Jarred Younger, to achieve a long sought after goal in this field: in this case identifying an autoimmune subset in ME/CFS. Her success, thus far, has spawned other studies. At the Stanford Symposium Dr. Jonas Bergquist reported that he’d validated her autoimmune antibody results in a larger ME/CFS cohort. Plus doctors in the U.S. and elsewhere are using her antibody tests to assess their patients.
Score another win for the 2016 Ramsey Awards.
Conclusion
With four of the five 2016 Ramsey Awards producing successful results and follow up grant applications, awards, studies and publications, the 2016 Ramsay group has done amazingly well. In fact it may be in a class of its own. It certainly demonstrates how valuable pilot studies can be.
When pilot studies work they can produce a massive return on investment
Let’s assume that Younger gets his big NIH grant, plus he scored another grant on neuroinflammation from MERUK. The Cambridge-Mensah group has received another grant and Prusty is applying for one. Plus Scheibenbogen’s autoimmune work has spawned a large outside study.
In dollar terms alone, by the end of this year the SMCI’s $250K investment in 2016 may have brought in something like $5 million in new ME/CFS funding with more, hopefully, to come. Plus it’s brought several new researchers into the field. In short, if you contributed financially to these awards, pat yourself on the back – you made an excellent investment.
The biggest problem the SMCI may have right now is the very high bar the 2016 group set. We should know if lightning has struck twice soon. We should be hearing from the 2017 Award winners over the next six months or so and the 2018 Ramsay Award winners will be announced soon.
Want more grant applications? Here’s an idea – fund more Ramsay Awards….Find out more about them here.
Has anyone tried to measure the level of lymphocytes in the CFS brain? There is a gut illness called lymphocytic colitis and I wonder if CFS/fibro might be a form of ‘clogging up the brain’ with a constant inrush of lymphocytes to attack such herpesviruses or other toxins/pathogens as may be there, or, as perhaps in colitis, rushing in in error when there is nothing there needing this immune response, or this level of immune response.
Nice idea! Those lymphocytes can cause major problems in the brain. You’ll be happy to know that Jarred Younger is using a grant award to study just that. If that study is successful expect another multi-million dollar grant. That’s the power of pilot studies – we need more of them!
Check out this blog – https://www.healthrising.org/blog/2018/09/25/invasion-neuroinflammation-chronic-fatigue-syndrome/for more.
All this research is almost completely pointless as it is not coordinated. We need an organisation, department or individual that can start with a clean sheet of paper and consider ME/CFS as a whole rather than through the prism of their own specialism.
Well, I agree that organization is a good thing and while I would like to see a coordinated, kind of master strategy to ME/CFS that’s rarely done in any disease. It’s just not how the NIH or medical research usually works.
The NIH works by awarding individual researchers. It may inefficient at times but it also allows for a lot of creativity. You can get boxed in by a master plan but allowing any researcher to able to apply for a grant allows for maximum creativity.
Could it be better? Sure. But it’s also responsible for countless breakthroughs in medicine. Take the Prusty Award. Who knew that Prusty could produce a finding that HHV-6 finds a way to inhibit the mitochondria of adjacent cells?
Take the Scheibenbogen award – that helps us build the case for an autoimmune subset. If we had a master plan for ME/CFS it would surely include doing that.
Same with Jarred Younger – proving neuroinflammation exists would be at the very top of the list of any master plan. So, something of a master plan is getting done – without having a master plan 🙂
Several Herpes type virus can increase oxidative stress. That is enough to partially switch the microchondia from one cell from producing work to producing hydrogen peroxide. That is among others switching a cell to CDR.
If confirmed, Prusty’s finding that a single Herpes virus infected cell can trigger neighboring cells may be very important.
We already know Herpes viruses love to reactivate when other infections are present. They seem to abuse the preoccupation of the immune system to multiply before they go dormant again.
Thinking a bit further on it, it may well be the virus doesn’t cause a false alarm nor is even triggering the alarm itself. Also, there may be no elusive marker that triggers this state. Let me explain:
* Herpes viruses are amongst the utmost successful human viruses; 80 to 90% of adult humans for examples carries EBV for example and allows most of them to reach a healthy old age.
* Such successful viruses have been largely able to escape the immune system for thousands of years, where immunity adapts to most viruses in weeks.
* Unlike Aids, Herpes viruses don’t escape the immune system by continuously varying and evolving at a very rapid pace. And even against Aids some people do have natural immunity. Without medicine, people with this immunity would be selected and humanity might largely over win this disease like it did with colds, the flue…
* Having a single simple signal molecule shutting down nearby mitochondria or using a single signal molecule to trick the immune system to over respond would very likely have been countered by the immune system a long time ago.
What would work better from the point of view of the virus?
* Something with plenty of variation so that the immune system can’t adapt to.
* Something activating the immune system that doesn’t leave a direct trace to the virus itself.
* Something that causes an immune reaction to something else then to viruses, that would allow the virus to spread even easier undetected.
* Something that has only a moderate chance of killing the host early and does leave few permanent damage.
* Something that can signal both the infected cell as well as neighboring cells to go into CDR.
=> Something like the virus causing protein misfolding rates to go up significant but not to an extreme extend would be a fairly good first candidate to fit that bill:
* Misfolded proteins are near perfectly random; it’s impossible for the immune system to counteract a specific molecule.
* Misfolded proteins occur in any healthy person and hence leave very few trace to a virus hiding in a cell.
* It would cause an immune reaction to misfolded proteins. That is taken care of mainly by the innate immune system and NETosis. NETosis creates a lot of inflammation, ROS, capillary blocking and so on. Near perfect conditions for Herpes viruses to reactivate.
* As somehow Herpes viruses have the ability to avoid being catched by the adaptive immune system, it has to fear the innate immune system the most. Keeping that preoccupied with misfolded proteins is a strong strategy.
* A reaction to misfolded proteins does increase chances for auto immunity diseases a lot, as is seen in ME.
* Far too large amounts of misfolded proteins can increase chances of getting cancer, as is seen in a subgroup of ME patients.
If something like that would occur, it would explain both why there are so few specific biomarkers for ME and why so few permanent damage is seen while at the same time it would explain why the body has to shut down in body wide CDR.
It would make it very hard to find the elusive molecule switching our cells to CDR and so make that a difficult target for treatment. Switching off the CDR as if it were a false signal would be a poor option too.
But such a successful virus has no “desire” to make the patient sick. So it only wants to preoccupy the immune system without depleting it. That is a good thing, as it would mean that we only get sick because several other factors increase the effect of things the Herpes viruses are doing, bringing the total effect out of control. Some like genetic factors would be hard to influence under these conditions. But others like undigested proteins entering the bloodstream could be tuned down. Just having more knowledge of what amplifies or reduces the effect of these viruses may be key to understanding how many of the partially successful self treatments work.
Interesting about herpes viruses liking to reactivate each other. I had forgotten about that.
Interesting idea about the misfolding proteins. Herpes viruses are clearly masters at what they do in order to survive in our bodies like they do – as so few viruses can. I imagine they still hold quite a few surprises for us.
Dejurgen, I will be rereading your post for days. As you will be reading mine for days if Cort decides to post this monstrosity of a response. Who are you? Your post above ??is one of the most thought provoking and informative posts in an ME or FMS forum that I have come across which addresses the potential role that herpes viruses can play in these illnesses. May I please pick your ? and use Cort’s forum to ask you some questions and emphasize a few quick points? First and foremost, ? off to you for focusing your analysis ?? from the “point of view” of the virus. Nice approach. ? I believe we should “personify”, for lack of a better word, these viruses. What are they trying to accomplish? Replication? Preoccupation of the immune system? Mutation and modification of the rDNA of T/B cells in order to enhance survivability? Are they safeguarding their replication process by Influencing the microbiome environment like insurgents? Are they blending in with the local populace? Where do they hide? Are they taking shelter in the root, dorsal, and perifrial ganglia of the CNS/PNS/ and Vagus Nerve? Are they migrating to organs such as the stomach, liver, and causing inflamation in the ?? ? .Dr Prusty and his team had taken tissue samples from organs of the deceased that revealed HHV6 rDNA. Herpes viruses are stealthy little creatures. Please bear with my counterinsurgency analogy. What are these insurgents doing to our cells? Are they putting them in danger response mode and creating oxidative stress like Dejurgen points out? Are they messing with our metabolism? If so, how do we combat them? In the case of potential treatment for Fibromyalgia, do we switch from a traditional SNRI approach to an anti-viral/anti inflammatory approach? Replace the Cymbalta/Savella with the Skip Pridgen Protocol (Acyclovir & Celebrex)? If so, which herpes viruses are we targeting? Do we go after EBV(type IV) and Cytomegalovirus(type V) and treat with Valcyte like I think Dr Jose Montoya is doing for some of his severe ME patients? Or do we go after, as in my case, VZV(Type III) and ZSH(Type III variation Sin Herpete? Hypothetically speaking, ? , what if a person has had IGG titers that revealed previous exposure to 6/8 of the herpes type viruses? Does that put him/her in the same category as the rest of the himan population? Or, can this increase the virulence or severity of his/her condition? What if this level of viral activity (primarily reactivation) leads to “succesive infection” (Amy Proal’s concept)? What if a person who has had Zoster reactivation 6 different times in the last ten years also comes down with C Difficile, Strongyloidiasis, and a plethora of other pathogenic infections? What if this chronic cycle of infection is causing continuous flu ? like fatigue and muscular pain? What if this person has had leukocytosis (high AB Neutro count and low lymphocytes outside the normal reference range for the last 5 years as biomarked in 20/25 CDC blood panels? Does this mean that the bacterial, parisitical, fungal, and viral infections that were once active and that reactivate from time to time have caused this person’s FMS and ME? Or is this person’s illness caused by something else entirely? Maybe this person has AIDS? However, tests for the last 28 years reveal this person is negative for HIV. This person has been diagnosed with FMS by a rheumatologist and a neurologist and his PCM diagnosed him with ME. Does exercise induce malaise or does it make this patient better? What if I told you this person is stuck in exercise purgatory? Damned if he/she does, damned if he/she doesn’t? My god, I’m killing you guys here. Where is my ? of thought? Is this ? fog or cognitive impairment that is causing me to babble like this or is it PTSD from 6 combat deployments in Iraq ?? and Afghanistan ??? Did my illness cause my depression or did depression cause my illness? Ok, enough. Let me switch gears and do so expediently before Cort bans me from this forum forever. Could amino acid, vitamins, minerals supplementation coupled with a high protein, low carb, moderate fat diet with controlled/medically supervised intermittent fasting help this person? This is what some patients turn to because they feel like their cells are starving for better health. Don’t try this at home unless under medical supervision and you should read some of what Cort posted about serotonin before you go down this road. However, I have to say that, so far, this approach has shown promise for him/her. I will conclude with this. What you have just witnessed is what happens to someone when they have been afflicted with FMS and ME for a very long time. I am not as severely afflicted as others, not even close, I will always remember this before I start feeling pity for myself! Regardless of the severity, however; these beasts of illnesses that have no identifiable etiology and that are accompanied with stigmatism and provide little answers drive us close to insanity! Fortunately, we all have Cort! I promise Cort to never ? your forum again and to ? to someone else speak moving forward. I hope somebody can gain something constructive from this post. Dejurgen, your feedback is greatly appreciated.
Hi Chris, I’ll try and answer some questions you have and maybe later this week some more. I’ll break it up in separate comments.
First: I have no single medical education, so consider my idea’s as layman’s thoughts.
So who I am? A layman with an engineering education, research background and a remarkable intuition that helped me a lot getting better once I allowed to rely on it. When I started trusting it, it went diagonally against about everything medical science stood for, so taking that leap of faith was not an easy one. Now, I use an expanding “reference frame” of thinking that collides very few with established medical science to my own surprise. Sometimes it’s necessary to take a long distance and detour to see radical different ideas reunite with what’s already their, but in an entirely unconventional new combination.
At a certain moment I had roughly 5% of functionality left and lost health and abilities by the week. At that moment I decided to leave everything I new and listen to my body and follow it however absurd it was. All that what was logical failed me badly. I had neither the education nor remaining mental abilities to reexamine all this work in detail to see what smart and highly educated people may have missed. So I decided to look into what was supposed to be impossible. Maybe their was some misplaced treasure their. And sure their was!
I’ve been unable at times to speak, recall my name, increasingly lost control over my muscles (had increasing rates of temporary paralysis events that lasted a few seconds each) and experienced both pain and exhaustion beyond what I ever imagined could exist when I was still healthy.
Now I am roughly at 20 to 25% of health and improving. Even the moderate abilities I have now are heaven compared to the hell I was in. I can’t even recall the pure agony I was in to a full extend back then anymore: it’s more then any normal being can recall when not experiencing it IMO.
As a last one: I am fond of my privacy. I am lucky to have disability insurance and I still badly need it. While I can produce very creative thoughts about this disease at some time, at others I fail to do basic thing like figgering out how to put two dishes in the oven to heat them up or speak in sentences… and few people can understand this combination.
“What are they trying to accomplish?”
That’s a difficult question. Your counterinsurgency analogy certainly is on of many ideas worth exploring. In such an unconventional disease I believe success depends on being able to leave previously held ideas and try out plenty alternatives to see how well they fit our reality.
Let me go back one more step: what are they?
Amongst others, they are players living in an ecosystem. If any entity lives long time stable (stable virus over many generations of humans) in an ecosystem I believe it has to both give and take. I know no exceptions of lasting stable one sided relationships in an ecosystem. Even humanity is (re)learning to give back to the world it is living in as it learns the hard way not doing so is not sustainable.
That does not mean each of those relationships seems attractive. Somewhere in North America for example the wolf went extinct by hunting. Within a few decades a very diverse ecosystem with a wide variety of forest, open places, plenty of fauna and flora changed to a very thinned and fragile ecosystem. Reintroducing a dozens or so of wolves slowly brought back the ecosystem. While they seem to only take by eating other animals, they provided a diverse ecosystem by encouraging grazers to move around a lot and that maintained a far higher biodiversity of plants. That was the wolves unintended way of giving back.
Why could this idea be important? As 80+ % of adult humans has EBV infection and that is only one of possible Herpes infections, it is safe to assume that far over 90% of human adults have some latent Herpes virus residing in them. In pre-industrial times with low access to clean water and hygiene, probably 99+% of 10 year old kids had some sort of Herpes infection.
We may well have co-evolved with Herpes viruses. In fact, human DNA does contain part of borrowed viral material that appeared to be a nice improvment in our evolution.
Just as much as there are bad bacteria like Salmonella and good like healthy gut bacteria (and probably some like Helicobacter pylori that has some properties of both), their may exist such viruses. And being something like a healthy gut bacteria that is treasured by our body certainly has some advantages.
The point of all of this is that we may function optimal when infected by some Herpes viruses at a young age. That was very likely the historical situation. The tight interaction of for some Herpes viruses with the immune system may make them to a certain extend part of our own immune system just like that the tight interaction of our gut with the healthy gut microbiome makes them a (essential) part of our digestive system.
While I take a low amount of Isoprinosine (aka Immunovir) and it was an instant success and I sometimes would like those retroviruses completely out of my body I doubt it would be the ideal situation.
I think having been infected by some Herpes virus at a young age is better then not being infected is better than being infected at adult age. And being able to reduce the extend of the infection may be as good as wiping it out in many cases when one takes the side-effects of taking very large amounts of antivirals into account.
Better still: try and find a way to let the body bring the number of Herpes infected cells into “optimal” range.
Any successful player in an ecosystem has co-evolved with the ecosystem a way to keep it’s numbers in check. Too few equals endangering it’s continued success/survival, too much endangers the ecosystem it lives in and feeds on.
Why is this idea important? Well as Herpes viruses have a very stable “relationship” with human beings, their numbers must be kept in check by both the viruses themselves as our own body. The multiplication rate of these viruses after initial infection are nothing compared to what is seen in disease like for example the flu. The flu is a disease in which every branch ends with self-destruction and that is clearly a different working model.
It’s easy to say that our immune system keeps the virus in check after initial infection. But that is far to simplistic. The virus itself has code to put itself dormant after initial infection. The term initial infection however is of value here. The virus isn’t a thinking being, so how does it know the current infection is the initial one? How does an infected cell knows this is not an initial viral infection and limits it replication speed? It seems to have some more tricks upon its sleeve.
The answer to the latter question I do not know. But after thinking a bit about your comment I could imagine that the CDR is part of the replication rate self control mechanism. A CDR reaction does slow down viral replication rates. If a single infected cell can turn down the mitochondria of not only the cell it resides in but also the neighboring cells then one (or some) infected cell could effectively slow infection of a nearby cell with a Herpes virus (or another virus) a lot. If so, forcefully disabling CDR as it is believed to be a faulty immune response could backfire big time for some patients.
It could also explain why nerves (and brain if it gets there?) are particularly vulnerable to EBV, Zoster,… If this mechanism were there, it would give healthy non-Herpes-infected cells a bigger division rate then infected ones. In fast regenerating tissue that may well help to reduce Herpes infection rates if they are above “optimal”. As nerves renew far slower that option may be unavailable. As such, it may be not that surprising that MS is the prime disease where EBV seems into play: once nerves are “over-infected” they remain so for a long time and may be a long lasting “focused” source of nasty stuff the immune system has to fight to. That should lower the threshold to auto immunity to nerve tissue.
My relating opinions to your questions:
* 6 Herpes infections may be less severe then 6 times an infection by a single Herpes virus, but worse then an infection by a single Herpes virus.
* In fast regenerating tissue like calves, arm muscles (regarding FM) the better option might be to try and avoid reactivation of the Herpes viruses if the “self-control” mechanism would reduce numbers there.
* The more difficult ones may be located in the nerves. Counter to previous believes they do regenerate faster than not-at-all so that is a plus. Reducing their numbers may be where to focus the effort. Maybe some meds can focus that effort? * Somehow gently improving blood circulation did strongly reduce my nerve pain. I doubt it got my Herpes viral count there down a lot, but maybe it did get local reactivation down a lot?
* To add to the latter, gently improving local blood flow by doing daily circulation exercises has helped me a lot with plenty of symptoms. Consult an experienced PT for guiding.
I myself have got EBV at adult age, got cold sores (HHV-1) first at adult age ans somehow recognize the image of Zoster I looked into after reading your comment, again at adult age so 2-3 Herpes viruses caught at young adult age.
“What if a person who has had Zoster reactivation 6 different times in the last ten years also comes down with C Difficile, Strongyloidiasis… …What if this person has had leukocytosis (high AB Neutro count and low lymphocytes outside the normal reference…”
From reading your comment it seems you say that the Zoster reactivations were before the other things, but from reading the list I would think you had likely that Strongyloidiasis or maybe that C Difficile infection already for a really long time too, like saying since about at least the last 4 Zoster reactivations. Would that assumption be correct?
Not knowing Strongyloidiasis, I looked it up at wikipedia.
“Strongyloides infection occurs in five forms. As the infection continues and the larvae matures, there may be respiratory symptoms (Löffler’s syndrome). The infection may then become chronic with mainly digestive symptoms. On reinfection (when larvae migrate through the body) from the skin to the lungs and finally to the small intestine, there may be respiratory, skin and digestive symptoms. Finally, the hyperinfection syndrome causes symptoms in many organ systems, including the central nervous system.”
* First affecting respiration: ME “supporting” check!
* Second infecting digestive tract: ME “supporting” check!
* In the small intestine? ME “supporting” check!
* Finally, the hyperinfection syndrome causes symptoms in many organ systems, including the central nervous system. => that may be the result of the bugger long time reactivating your plethora of Herpes viruses. They (Herpes) seem to have a tendency to overpopulate the nerves.
After looking up C Difficile and seeing the nasty pictures I combined it with the Strongyloides thing and something I recently learned.
I have no serious allergy whatsoever. I thought I had no single food intolerance neither until a few months ago. I tried before to exclude some foods for a period of time to see if it had any effect: none at all. Now it appears to be because I have a long list of food intolerances so while excluding one food I still ate maybe over half of my diet stuff I was intolerant too.
Due to some other “health choices” I did eat few bread and very few fruit safe for some papaya. I did get fibers from increasing the consumption of some vegetables. In short, I happened to have eaten few fruit and near zero apples for quite some time.
As I learned that somehow I had a lot of trouble with undigested proteins, and some close relatives have a long list of food they have troubles with (but are not sick of) I slowly tried to find out what food is safe enough to keep for composing an exclusion diet. Having a daily aggressive food in their isn’t helpful. Too my strong surprise I reacted very strongly to eating two small apples as breakfast. Apples are supposed to be very healthy and digest well. While my mother said she had no real problem with apples herself, she still added that eating two small apples, even if they were combined no bigger then a normal apple, and nothing next to it as a breakfast is a bad idea. So she likely has the same problem to a lesser extend.
Symptoms? The same evening diarrhea and blood in the stool. It wasn’t a pool but it sure was more then a few drops! And pain was somewhere below my stomach so it likely took a big route where it could get lost. If so, the origin was the small intestine and it was more then a bit of micro-damage.
On one side all scientific elements for leaky gut syndrome do exist, on the other hand many doctors dismiss the idea of leaky gut. So I was careful giving the idea an important place. Seems however that it required far more then some microscopic damage to cause a small continues stream of blood to reach the toilet. Think about carved/scarred bleeding gut!
It took me over a month of a far more strict diet then I used before to get the constant swinging between constipation and diarrhea and the gut pain mostly under control. It took about two weeks to get the blood in stool every other day stopping. I had all the above symptoms for many many years before getting sick. It actually ended, together with frequent nose bleedings, when I got down with ME/FM. That was probably due to lack of sufficient blood, blood flow and pressure. Wounds didn’t bleed any more like they used to before ;-). Having improved health recently nose bleedings popped up to some extend again: a sign of increased blood volumes?
Two tiny apples caused over a month of problems! Didn’t imagine that before.
However it is a good candidate for an “ME-enhancer”:
* loss of blood decreases already low blood volumes
* entrance of bacteria, bacterial toxins… into the blood stream causing/needing a very strong immune reaction that is largely body wide; can trigger Herpes reactivation on a daily basis
* entrance of partially undigested proteins. Needs a strong reaction of Neutrophils through the effect of NETosis https://en.wikipedia.org/wiki/Neutrophil_extracellular_traps; see link with your leukocytosis! That alone could take one down IMO!
* entrance of gut content into the bloodstream through large wounds is a good recipe for “mild sepsis” as ME is sometimes compared to
=> Would you happen to also have frequent aphthous ulcers (a so called benign (auto?)-immune disease) and/or adult acne? If so check my “improvement by eating papaya” topic on the diet section in the forum; consult a doctor if trying and please report results If you would try. Papaya also can reduce gut parasite counts.
In my case, fructose malabsorption seems to be a major offender. It’ll take a long time for me to find all of them. I would be very unsurprised if you had many potentially undiagnosed food intolerances too.
Dejurgen,
? for your feedback and answering a question. I love the segment approach because there is so much to cover.
*I’ve always viewed an engineer as the link between science and application. Any person with an engineer education and a researcher’s background is someone I am interested in listening ? to. However, if an engineer or researcher dismisses the value and power of intuition, I usually look elsewhere for insight. I think some people who hold these backgrounds forget what Einstein and Emerson taught us about intuition. Finally, what impresses me the most about your background is that you are a layman and a patient. You have experienced firsthand what this illness is like. Heredity and environment are no substitutes for personal experience. Some people place overemphasis on these two factors when assessing a person’s intellectual and educational capacities.
*Your “reference frame” approach is intriguing. I use science, physics, and Einsteinian Relativity to analyze my illness. However, I do not concur with the notion that one does not have to be on the train ? to observe it. Let me explain how I interpret what you said. I cocur ? that we should parallel the train and observe it from an outside reference frame ? when analyzing established traditional science and medicine, kind of like the way a satellite ? does when measuring location to known reference points on the Earth ? or when pointed toward the “ ⭐️ s “. Yet, when it comes to analyzing transformation, I believe, this has to come from within, introspectively, as a passenger aboard the train ?. Each patient is different. Each patient is a primary, as opposed, to secondary source about what is occurring in their bodies. Speaking of bodies…
**”Listen to your body.” ?. What you convey here is often undervalued and underutilized. Most of us fall into the trap of waiting for a ?? scientist, researcher ??, doctor ?⚕️, or “SME” to tell us which treatment approach is right or wrong. This, for me personally, is often perceived as insulting. Just because I do not come from the world of academia does not mean I can’t fathom what is going on inside my body and take necessary action to treat and troubleshoot my condition. I’d rather die trying than sit back and wait for permission from someone who can’t possibly understand what I am going through regardless of their educational or professional background. We only have so many days remaining on this earth ? and I’d rather experiment trying to improve the QOL of my life and that of my family’s rather than waiting for effective treatment or a possible cure. What is that saying? ?? I paraphrase, “Ignorance is doing the same thing over and over again and not achieving results.”
*When you hit 5% of functionality, it is my impression that your instinct to survive surpassed “everything you knew” and set you on a different path no matter “how absurd” it might be portrayed. If you didn’t do this, you might be dead ? by now either via suicide or via succumbing to your illness. Either way having 5% functionality is a hard way to live. Just take a look at how many fallen heroes have taken their own lives in the ME/FMS community. Devastating.
*Which leads me to inquire, what is this “misplaced treasure” you allude to? Is this treasure the “approach” itself or an actual object that you incorporated into your treatment regimen?
*Cognitive dysfunction happens to me all the time. At first, I noticed a digression in the ability to verbally articulate and communicate with others. Later, it progressed and manifested itself in my inability to communicate effectively via written words. Some days are good. Some days are bad. Yet, like you, I still have moments of clarity and can provide constructive feedback and contributions to discussion. It is when I place folded clothes in the kitchen pantry or place trash ? in the kitchen oven that I begin to worry. I say this literally and not figuratively. These things actually happened. This is one of the reasons I have decided to target ? neurotransmitter health and why I supplement with amino acids, vitamins, and minerals.
*Dejurgen, I wish I knew your real name, thank you for your feedback. I hope it continues throughout the week. I do respect and value your privacy. I have a feeling it wasn’t easy for you to ellaborate about your personal background. Thank you ? for sharing! Would you like to know who I am or should we move to the next segment? Scratch that, let’s move on to the next segment! ?. I talk too much. I want to ? more from you! With that said…
*I wouldn’t worry too much about tying up this thread. Take another look at Cort’s title. People afflicted with our illness, not all of them but most of them, are not that interested in the accolades that scientists receive or the funds they may be granted for further research. They are primarily interested in reading about more effective treatment and finding potential cures. Yet, if people took the time to read Cort’s subtitle to this article, it may wind up being a little crowded in here. However, people rarely take the time to examine the fine print. I’m glad I did or I never would have stumbled across you. ?
I’ll stray easily from the main topic, but always try to relate to it somehow. In this case: how could Herpes shut down the mitochondria, how does it effect us and how could we put ideas to use?
It may be true that some topics are less commented on, but I certainly do appreciate his wide choice of news coverage and so do many other people. If he only wrote about what helps us today there would not be much blogs on Healthrising would there?
I try and turn ideas in a further stage of development into topics on the forum. I only have one yet but plan to add several more. I tend to wait until ideas and observations get settled. I have a feeling we’ll meet there in the future ;-).
Around 2020 I hope to have put out a little booklet on how I improved from 5% to 50+% and be able to give a fairly consistent and reasonable explanation as to what worked and why it did. The goal is not to solve ME as I can’t, but to get a fair amount of logic and clarity in the many things that work from time to time to improve patients health.
Maybe you already reminded me on falling back to intuition if logic and intuition conflict. When logic is firm but intuition disagrees the latter tends often to be the safer bet. In this case: I’ve got a “nagging” feeling that part of the pain caused by fructose consumption is in the stomach itself, on top of the pain in the gut and adrenals. For internal organs it’s sometimes a bit tricky to identify if pain comes from the upper part of the gut or from the stomach. I dismissed it quite a few times as it did made not a bit of sense. After revisiting the topic of food intolerances and heliobacter pylori I might be able to connect a few extra dots that could clarify a few more unexplained things. Those are my treasures: things that made no sense whatsoever changing into far more logical units that give pointers on how to improve health yet another bit. If it works out after sinking in and checking I’ll put a comment on it on the papaya topic.
Dejurgen,
Thank you ? for your feedback addressing question #1, “Who are you?” Please see my response I posted last night. It has been a pleasure to meet you!
I just finished completing a response to segment 2, “What are they [trying to accomplish]?” and lost it in cyberspace. ? Here we go again, attempt #2. ??
“Players living in an ecosystem” – I love this description and the “wolves” analogy but let’s not forget, the exosystem was provided by the host. I did not invite this roommate into my home. However, now that he is living in my domicile, I need to learn how to “coexist.” Kind of like Felix Unger and Oscar Madison. There is a “give and take” relationship that exists. Maybe we aren’t at war? Thank you for bringing optimism to the duscussion. I will reevaluate my counterinsurgency analogy. “Tight interaction.” The immune system and the virus need to get along. I just hope the virus doesn’t try to change the immune system too much in an attempt to take over the house ?. However, why would it? If the host dies, then the virus dies and with that the home (ecosystem) gets demolished. In some rare cases, this actually occurs. Researchers have found herpes viruses In the DNA of the deceased’s vital organs such as the liver and the brain ?. The ecosystem became imbalanced. The odd couple could not get along. The host died.
*”We may function optimal when infected by some herpes viruses at a young age.” Is this because we will have more time to learn to coexist and evolve? At an older age, are we at a disadvantage because of the oxidized stress introduced by free radicals? ??
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249911/
We need to learn how to keep the ecosystem balanced. What we ingest in our bodies can help achieve this objective.
*Isoprinosine. Ahh this intrigues me. Immune booster? I have supplemented with Vitamin C, Glutathione, Melatonin, and a plethora of other supplements and minerals. I have also incorporated a nutritional plan that is very similar to the one you describe(more to follow in an upcoming post). I have never tried Immunovir. The name suggests antiviral origin and hints at anti-replication. I will do some research on this medication. ?. Right now I have been experimenting with L-Lysine but it competes for absorption with L-Arginine and I read somewhere that L-Arginine can enhance and promote herpes virus replication. I recently switched from L-Arginine to L-Citrulline and this seems to be working well. My intuition tells me that blood circulation is also important to the immune system/virus relationship so I am encouraged by your suggestion that an optimal coexistence can exist between the two. No steroids ever!
*I wish you could have seen my earlier response to this thread! It was much more qualitative, informative, and well written. I have to pace myself when responding to your feedback so please ? with me. Take comfort in the fact that you are helping me Dejurgen. I hope I can reciprocate and “replicate” this in the near future! ?
Dejurgen,
Your feedback has helped tremendously. I just spent 4 hours packaging a detailed response to segment 3 and again lost it in cyberspace. I’m ? and ? at the same time. I’ll work on it again soon and this time save it on my computer ? rather than construct it on my smartphone ?. You are an extremely intuitive and intelligent person. ? so much! Cort, thank you for allowing us to use this platform to communicate.